TNFα genotype influences development of IgA-ASCA antibodies in Crohn's disease patients with CARD15 wild type

A typical feature of Crohn's disease (CD) patients is the development of antibodies against self - (PAB) or exogenous (ASCA) antigens, a process in which mucosal cytokine expression pattern might be involved. On the other hand, mutations in CARD15, a genetic risk factor for CD, alter cytokine production in response to bacterial. infection. In the present study, we evaluated the rote of functionally relevant IL-10 and TNF alpha gene polymorphisms in the synthesis of these antibodies and their relationship with CARD15 mutations. In CARD15 wild type patients, high TNFa producer genotypes protect against IgA-ASCA development, whereas an inverse association was observed in autoantibody synthesis (PAB). These associations were not observed in patients with CARD15 mutations, probably due to the Lack of TNF alpha release as a consequence of the failure of CARD15 protein to recognize the peptidoglycan. Thus, we proposed a CARD15-TNF alpha circuit that might play a role in mucosal immune surveillance. (c) 2006 Elsevier Inc. All rights reserved.